Effects of TiO₂ nanoparticles on the physicochemical and biological properties of oxidized sodium alginate/polyacrylamide-gelatin composite hydrogels fabricated by interpenetrating network approach

To enhance the applicability of alginate hydrogel in tissue engineering, we attempted to fabricate oxidized sodium alginate/polyacrylamide-gelatin (OSA/PAM-GT) composite hydrogels by interpenetrating network approach with the hydroxyapatite/D-glucono-delta-lactone (HAP/GDL) as the endogenous ionic cross-linking agent for oxidized sodium alginate (OSA) and N, N '-methylenebisacrylamide (MBAA) as the chemical cross-linking agent for polyacrylamide (PAM), followed by their surface coverage with gelatin. Then TiO2 nanoparticles as the reinforcing agent were added to the OSA/PAM-GT hydrogel matrix to construct organic/inorganic hybrid OSA/TiO2/PAM-GT composite hydrogels. In particular, the effects of the amount of TiO2 nanoparticles on the microscopic morphology, mechanical properties, swellability, biodegradability, bio-mineralization and biocompatibility of the composite hydrogels were studied. Experimental results indicated that the addition of TiO2 nanoparticles into the matrix of OSA/TiO2/PAM-GT composite hydrogels could effectively regulate the porosity, mechanical properties, swelling ratio, in vitro biodegradability and bio-mineralization of OSA/TiO2/PAM-GT composite. Moreover, OSA/TiO2/PAM-GT composite hydrogels had the best biocompatibility when the content of TiO2 nanoparticles was 0.5% (w/v), indicating that an appropriate amount of TiO2 nanoparticles could effectively promote cell adhesion, proliferation and differentiation. Consequently, the combined method of the interpenetrating network technology, the incorporation of TiO2 nanoparticles with the surface coverage of gelatin could overcome the defects of alginate hydrogels to some extent, making OSA/TiO2/PAM-GT composite hydrogels suitable for tissue engineering applications.